Carbon Nanotube Degradation in Macrophages: Live Nanoscale Monitoring and Understanding of Biological Pathway

Abstract

Despite numerous applications, the cellular-clearance mechanism of multiwalled carbon nanotubes (MWCNTs) has not been clearly established yet. Previous in vitro studies showed the ability of oxidative enzymes to induce nanotube degradation. Interestingly, these enzymes have the common capacity to produce reactive oxygen species (ROS). Here, we combined material and life science approaches for revealing an intracellular way taken by macrophages to degrade carbon nanotubes. We report the in situ monitoring of ROS-mediated MWCNT degradation by liquid-cell transmission electron microscopy. Two degradation mechanisms induced by hydroxyl radicals were extracted from these unseen dynamic nanoscale investigations: a non-site-specific thinning process of the walls and a site-specific transversal drilling process on pre-existing defects of nanotubes. Remarkably, similar ROS-induced structural injuries were observed on MWCNTs after aging into macrophages from 1 to 7 days. Beside unraveling oxidative transformations of MWCNT structure, we elucidated an important, albeit not exclusive, biological pathway for MWCNT degradation in macrophages, involving NOX2 complex activation, superoxide production, and hydroxyl radical attack, which highlights the critical role of oxidative stress in cellular processing of MWCNTs.

Biological interactions of carbon-based nanomaterials: From coronation to degradation

“…Evidence for NADPH oxidase-dependent degradation of SWCNTs in vivo was also provided [160]. Moreover, Zhang et al [161] reported that carbon nanohorns also undergo partial degradation in macrophage-like cell lines (RAW264.7 and THP-1) and degradation of MWCNTs has also been reported recently using differentiated THP-1 cells as a model [162]. Importantly, in the studies cited above, degradation was shown to occur in a complex biological environment, i.e., in cell culture in the presence of fetal bovine serum, or in the lungs of mice, suggesting that bio-corona formation does not prevent degradation of carbon-based nanomaterials.…”

Enzymatic oxidative biodegradation of nanoparticles: Mechanisms, significance and applications

“…However, O 2 − • and NO• can effectively react to yield peroxynitrite, whose oxidizing potency is sufficient to cause biodegradation (Ischiropoulos et al, 1992). In vitro , effective biodegradation capacity has been demonstrated for several types of macrophages such as RAW 264.7, THP-1, and human monocyte-derived macrophages (Kagan et al, 2014; Elgrabli et al, 2008, 2015; Zhang et al, 2015) (Table 1). Because peroxynitrite-dependent oxidation reactions are independent of the direct binding of the reactive protein intermediates with nanoparticles, the degradation process driven by macrophages is independent on the specific positioning of the oxidative machinery on the surface of nanoparticles.…”

Defect density in multiwalled carbon nanotubes influences ovalbumin adsorption and promotes macrophage activation and CD4^+ T-cell proliferation

“…Recent evidence has also reported the possibility of the degradation of CNTs by cells, such as neutrophils, 32 microglia, 33 and macrophages. [34][35][36] Overall, the current data suggest that the toxicity of MWCNTs can be at least partly reduced or minimized by improving design strategies of short-length MWCNT with appropriate surface modifications that are feasible for degradation by cells after the delivery of loaded proteins or drugs.…”